Phase II Study of Vismodegib in Patients With Refractory or Relapsed B-cell Lymphoma or Chronic Lymphocytic Leukemia

Inclusion Criteria: * Histologically confirmed diagnosis of B-cell lymphoma (DLBCL, MCL, FL, MZL, LPL/WM, SLL or PCNSL) or CLL (Matutes score ≥4) requiring treatment that is recurrent after at least one prior therapy for which no potentially curative therapy nor better treatment option is available. Specifically, the patient should have received all treatments considered to be standards of care, including stem cell transplantation (when appropriate, if patient eligible), and agents known to have significant clinical efficacy in their disease.Patient must be eligible for tumor biopsy. Biopsy at relapse is mandatory for all patients except for PCNSL (optional) and should provide enough tumor tissue for biological tests (paraffin-embedded and frozen or RNAlater-conserved tissue). * Age 18 and older * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 * Signed inform consent * Life expectancy ≥ 3 months * Patients who have received up to a maximum of 4 lines of treatment (including radiotherapy) * Patients must have recovered from all toxicities related to prior treatments to ≤ grade 1. * Adequate Laboratory Parameters (unless abnormalities are related to underlying disease) within 28 days prior to signing informed consent, including: * Absolute neutrophil count (ANC) ≥ 1000/μL * Platelet ≥ 75,000/μL * Hemoglobin \> 8.5 g/dL * Total bilirubin ≤ 1.5 x upper limit of normal (UNL) * Hepatic enzymes (AST, ALT) ≤ 3 x institutional ULN * Measurable disease: * Cohort 1 and 2 (DLBCL and iNHL): Bi-dimensionally measurable disease at CT scan with at least 2cm in their longest diameter. * Cohort 3 (PCNSL): Measurable PCNSL on MRI with gadolinium enhancement (no minimal size) or, for intraocular lymphoma (IOL), measurable disease at fundoscopic examination with elevated level of IL10 (\>10 pg/ml) in the acqueous humor. * Cohort 4 (CLL): Measurable disease assessable in the blood (lymphocytosis, cytopenia) and/or by imaging (bi-dimensionally measurable disease at CT scan with at least 2cm in their longest diameter) * Patient must be able to take oral medication * Females of childbearing potential (FCBP) must : * have a negative pregnancy test (serum or urine, sensitivity \< or = 25IU HCG/L) within 96 hours prior to starting study drug administration. * Agree to use two reliable forms of contraception or to practice complete abstinence from heterosexual contact during whole treatment period and up to 7 months after discontinuation of study drug treatment * Male patients must agree : * to use a condom with female of childbearing potential or to practice complete abstinence during whole treatment period and up to 7 months after discontinuation of study drug treatment. * To abstain from donating semen during whole treatment period and up to 7 months after discontinuation of study drug treatment * For all patients receiving vismodegib (GDC-0449): * To agree to abstain from donating blood during the whole study and for at least 7 months after discontinuation of study drug treatment * To agree not to share the study medication with another person Exclusion Criteria: * Pregnant or breastfeeding lactating females. * For CLL patients, clinically significant auto-immune cytopenia, Coombs-positive hemolytic anemia as judged by the treating physician * Concomitant anti-tumor therapy (e.g., chemotherapy, corticosteroids, other targeted therapy, radiation therapy). Corticosteroids may be authorized for PCNSL only during maximum 3 weeks (before and/or at the beginning of treatment with vismodegib) at a maximum dose of 1mg/kg of prednisone or equivalent. * Use of any standard or experimental anti-cancer drug therapy within 28 days prior to the study drug therapy (Day 1). * Patients with severe renal failure (creatinine clearance \< 30 ml/min according to Cockcroft \& Gault formula) and/or undergoing dialysis. Note: Patients with moderate renal insufficiency (i.e. creatinine clearance ≥ 30 ml/min) may be included. * Uncontrolled and/or unstable concomitant disease such as infection requiring treatment with intravenous antibiotics. * HIV positive serology * Active hepatitis B or C * History of other disease, metabolic dysfunction, physical examination, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the study results or to expose the patient to high risk from treatment complications. * Patients unable to comply with the protocol requirements according to the investigator